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1.
Biomed Res Int ; 2021: 6380141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33708990

RESUMO

The aim of this study was to investigate the therapeutic efficacy and safety of transplanting human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in the treatment of cartilage injury. First, the articular cartilage defect model in rabbits was constructed. Then, the identified hUCB-MSCs and rabbit bone marrow stem cells (rBM-MSCs) were transplanted into the bone defect, respectively, and the cartilage repair effect was observed by hematoxylin-eosin (HE) staining and immunohistochemistry. Besides, the glycosaminoglycan (GAG) content and biomechanics of the restoration area were also evaluated. In our study, hUCB-MSCs and rBM-MSCs exhibited typical MSC characteristics, with positive expressions of CD73, CD105, and CD90 and negative for CD45, CD34, CD14, and HLA-DR. After the transplantation of hUCB-MSCs and rBM-MSCs, the overall quality of cartilage tissue was significantly improved, and the recipients did not show significant side effects in general. However, the expression of matrix metalloproteinase-13 (MMP-13) in the de novo tissues of the hUCB-MSCs and rBM-MSCs groups was both increased, indicating that the novel tissues may have some potential osteoarthritic changes. In conclusion, our results suggest the therapeutic effect of hUCB-MSCs transplantation in cartilage regeneration, providing a promising future in the clinical treatment of cartilage injury.

2.
Orphanet J Rare Dis ; 15(1): 288, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054853

RESUMO

BACKGROUND: Isolated macrodactyly is a severe congenital hand anomaly with functional and physiological impact. Known causative genes include PIK3CA, AKT1 and PTEN. The aim of this study is to gain insights into the genetics basis of isolated macrodactyly. RESULTS: We enrolled 24 patients with isolated macrodactyly. Four of them were diagnosed with Proteus syndrome based on skin presentations characteristic to this disease. Targeted next-generation sequencing was performed using patients' blood and affected tissues. Overall, 20 patients carry mosaic PIK3CA pathogenic variants, i.e. p.His1047Arg (N = 7), p.Glu542Lys (N = 6), p.Glu545Lys (N = 2), p.His1047Leu (N = 2), p.Glu453Lys (N = 1), p.Gln546Lys (N = 1) and p.His1047Tyr (N = 1). Four patients who met the diagnostic criteria of Proteus syndrome carry mosaic AKT1 p.Glu17Lys variant. Variant allele frequencies of these mosaic variants obtained through next-generation sequencing range from 10 to 33%. In genotype-phenotype correlation analysis of patients with PIK3CA variant, we found that patients with the macrodactyly of the lower limbs tend to carry PIK3CA variants located in the helical domain (P = 0.005). CONCLUSIONS: Mosaic PIK3CA and AKT1 variants can be found in all of our samples with isolated macrodactyly. Insights into phenotypic and genetic spectrum of isolated macrodactyly may be helpful in perusing a more precise and effective management of isolated macrodactyly.

3.
Orphanet J Rare Dis ; 15(1): 250, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933559

RESUMO

BACKGROUND: We previously reported a novel clinically distinguishable subtype of congenital scoliosis (CS), namely, TBX6-associated congenital scoliosis (TACS). We further developed the TBX6-associated CS risk score (TACScore), a multivariate phenotype-based model to predict TACS according to the patient's clinical manifestations. In this study, we aimed to evaluate whether using the TACScore as a screening method prior to performing whole-exome sequencing (WES) is more cost-effective than using WES as the first-line genetic test for CS. METHODS: We retrospectively collected the molecular data of 416 CS patients in the Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study. A decision tree was constructed to estimate the cost and the diagnostic time required for the two alternative strategies (TACScore versus WES). Bootstrapping simulations and sensitivity analyses were performed to examine the distributions and robustness of the estimates. The economic evaluation considered both the health care payer and the personal budget perspectives. RESULTS: From the health care payer perspective, the strategy of using the TACScore as the primary screening method resulted in an average cost of $1074.2 (95%CI: $1044.8 to $1103.5) and an average diagnostic duration of 38.7d (95%CI: 37.8d to 39.6d) to obtain a molecular diagnosis for each patient. In contrast, the corresponding values were $1169.6 (95%CI: $1166.9 to $1172.2) and 41.4d (95%CI: 41.1d to 41.7d) taking WES as the first-line test (P < 0.001). From the personal budget perspective, patients who were predicted to be positive by the TACScore received a result with an average cost of $715.1 (95%CI: $594.5 to $835.7) and an average diagnostic duration of 30.4d (95%CI: 26.3d to 34.6d). Comparatively, the strategy of WES as the first-line test was estimated to have significantly longer diagnostic time with an average of 44.0d (95%CI: 43.2d to 44.9d), and more expensive with an average of $1193.4 (95%CI: $1185.5 to $1201.3) (P < 0.001). In 100% of the bootstrapping simulations, the TACScore strategy was significantly less costly and more time-saving than WES. The sensitivity analyses revealed that the TACScore strategy remained cost-effective even when the cost per WES decreased to $8.8. CONCLUSIONS: This retrospective study provides clinicians with economic evidence to integrate the TACScore into clinical practice. The TACScore can be considered a cost-effective tool when it serves as a screening test prior to performing WES.

4.
J Med Genet ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381727

RESUMO

BACKGROUND: Early-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Identification of the molecular aetiology underlying patients with EOS could provide valuable information for both clinical management and prenatal screening. METHODS: In this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and their available family members (totaling 670 subjects). Another cohort of 13 patients with idiopathic early-onset scoliosis (IEOS) from the USA who underwent ES was also recruited. RESULTS: After ES data processing and variant interpretation, we detected molecular diagnostic variants in 92 out of 447 (20.6%) Chinese patients with EOS, including 8 patients with molecular confirmation of their clinical diagnosis and 84 patients with molecular diagnoses of previously unrecognised diseases underlying scoliosis. One out of 13 patients with IEOS from the US cohort was molecularly diagnosed. The age at presentation, the number of organ systems involved and the Cobb angle were the three top features predictive of a molecular diagnosis. CONCLUSION: ES enabled the molecular diagnosis/classification of patients with EOS. Specific clinical features/feature pairs are able to indicate the likelihood of gaining a molecular diagnosis through ES.

5.
Elife ; 92020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186512

RESUMO

Mechanical forces are fundamental regulators of cell behaviors. However, molecular regulation of mechanotransduction remain poorly understood. Here, we identified the mechanosensitive channels Piezo1 and Piezo2 as key force sensors required for bone development and osteoblast differentiation. Loss of Piezo1, or more severely Piezo1/2, in mesenchymal or osteoblast progenitor cells, led to multiple spontaneous bone fractures in newborn mice due to inhibition of osteoblast differentiation and increased bone resorption. In addition, loss of Piezo1/2 rendered resistant to further bone loss caused by unloading in both bone development and homeostasis. Mechanistically, Piezo1/2 relayed fluid shear stress and extracellular matrix stiffness signals to activate Ca2+ influx to stimulate Calcineurin, which promotes concerted activation of NFATc1, YAP1 and ß-catenin transcription factors by inducing their dephosphorylation as well as NFAT/YAP1/ß-catenin complex formation. Yap1 and ß-catenin activities were reduced in the Piezo1 and Piezo1/2 mutant bones and such defects were partially rescued by enhanced ß-catenin activities.

6.
Hum Mutat ; 41(1): 182-195, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31471994

RESUMO

Congenital scoliosis (CS) is a birth defect with variable clinical and anatomical manifestations due to spinal malformation. The genetic etiology underlying about 10% of CS cases in the Chinese population is compound inheritance by which the gene dosage is reduced below that of haploinsufficiency. In this genetic model, the trait manifests as a result of the combined effect of a rare variant and common pathogenic variant allele at a locus. From exome sequencing (ES) data of 523 patients in Asia and two patients in Texas, we identified six TBX6 gene-disruptive variants from 11 unrelated CS patients via ES and in vitro functional testing. The in trans mild hypomorphic allele was identified in 10 of the 11 subjects; as anticipated these 10 shared a similar spinal deformity of hemivertebrae. The remaining case has a homozygous variant in TBX6 (c.418C>T) and presents a more severe spinal deformity phenotype. We found decreased transcriptional activity and abnormal cellular localization as the molecular mechanisms for TBX6 missense loss-of-function alleles. Expanding the mutational spectrum of TBX6 pathogenic alleles enabled an increased molecular diagnostic detection rate, provided further evidence for the gene dosage-dependent genetic model underlying CS, and refined clinical classification.

7.
Mol Genet Genomic Med ; 8(1): e1023, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774634

RESUMO

BACKGROUND: The molecular and genetic mechanisms by which different single nucleotide variant alleles in specific genes, or at the same genetic locus, cause distinct disease phenotypes often remain unclear. Allelic truncating mutations of FBN1 could cause either classical Marfan syndrome (MFS) or a more complicated phenotype associated with Marfanoid-progeroid-lipodystrophy syndrome (MPLS). METHODS: We investigated a small cohort, encompassing two classical MFS and one MPLS subjects from China, whose clinical presentation included scoliosis potentially requiring surgical intervention. Targeted next generation sequencing was performed on all the participants. We analyzed the molecular diagnosis, clinical features, and the potential molecular mechanism involved in the MPLS subject in our cohort. RESULTS: We report a novel de novo FBN1 mutation for the first Chinese subject with MPLS, a more complicated fibrillinopathy, and two subjects with more classical MFS. We further predict that the MPLS truncating mutation, and others previously reported, is prone to escape the nonsense-mediated decay (NMD), while MFS mutations are predicted to be subjected to NMD. Also, the MPLS mutation occurs within the glucogenic hormone asprosin domain of FBN1. In vitro experiments showed that the single MPLS mutation p.Glu2759Cysfs*9 appears to perturb proper FBN1 protein aggregation as compared with the classical MFS mutation p.Tyr2596Thrfs*86. Both mutations appear to upregulate SMAD2 phosphorylation in vitro. CONCLUSION: We provide direct evidence that a dominant-negative interaction of FBN1 potentially explains the complex MPLS phenotypes through genetic and functional analysis. Our study expands the mutation spectrum of FBN1 and highlights the potential molecular mechanism for MPLS.

8.
Comput Struct Biotechnol J ; 17: 954-962, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31360334

RESUMO

Genetic factors play a substantial role in the etiology of skeletal diseases, which involve 1) defects in skeletal development, including intramembranous ossification and endochondral ossification; 2) defects in skeletal metabolism, including late bone growth and bone remodeling; 3) defects in early developmental processes related to skeletal diseases, such as neural crest cell (NCC) and cilia functions; 4) disturbance of the cellular signaling pathways which potentially affect bone growth. Efficient and high-throughput genetic methods have enabled the exploration and verification of disease-causing genes and variants. Animal models including mouse and zebrafish have been extensively used in functional mechanism studies of causal genes and variants. The conventional approaches of generating mutant animal models include spontaneous mutagenesis, random integration, and targeted integration via mouse embryonic stem cells. These approaches are costly and time-consuming. Recent development and application of gene-editing tools, especially the CRISPR/Cas9 system, has significantly accelerated the process of gene-editing in diverse organisms. Here we review both mice and zebrafish models of human skeletal diseases generated by CRISPR/Cas9 system, and their contributions to deciphering the underpins of disease mechanisms.

9.
Infection ; 47(3): 377-385, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30298471

RESUMO

BACKGROUND: Recent studies have suggested a possible association between respiratory infection and the use of inhaled corticosteroids (ICS). We aimed to ascertain the risk of upper respiratory tract infection (URTI) with long-term inhaled corticosteroid use among patients with asthma. METHODS: Through a comprehensive literature search of PubMed, Cochrane Library, EMBASE, and Google Scholar from inception to May 2018, we included randomized controlled trials of any ICS vs. a control treatment for asthma, with reporting of URTI as an adverse event. We conducted meta-analyses by the Peto approaches to generate summary estimates comparing ICS with non-ICS treatment on the risk of URTI. RESULTS: Seventeen trials (15,336 subjects) were included. Compared with non-ICS treatment, ICSs were associated with a significantly increased risk of URTI (Peto OR, 1.24; 95% CI 1.08-1.42; I2 = 5%, p = 0.002). Subgroup analyses were performed for different dose, both high- and low-dose ICSs were associated with a significantly increased risk of URTI (high dose: Peto OR, 1.46; 95% CI 1.05-2.03; I2 = 0%; p = 0.03) (low dose: Peto OR, 1.20; 95% CI 1.04-1.39; I2 = 25%; p = 0.01). Moreover, fluticasone was observed with an increased risk of URTI (Peto OR, 1.18; 95% CI 1.02-1.38; p = 0.03; heterogeneity: I2 = 21%) but not budesonide, low-dose fluticasone treatment was associated with a significantly higher risk of URTI but not high dose. CONCLUSIONS: This study raises safety concerns about the risk of URTI associated with ICS use in patients with asthma, but it should be further investigated.


Assuntos
Corticosteroides/efeitos adversos , Infecções Respiratórias/epidemiologia , Administração por Inalação , Asma/complicações , Relação Dose-Resposta a Droga , Humanos , Incidência , Infecções Respiratórias/induzido quimicamente
10.
Hum Mol Genet ; 28(4): 539-547, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30307510

RESUMO

Congenital vertebral malformations (CVMs) are associated with human TBX6 compound inheritance that combines a rare null allele and a common hypomorphic allele at the TBX6 locus. Our previous in vitro evidence suggested that this compound inheritance resulted in a TBX6 gene dosage of less than haploinsufficiency (i.e. <50%) as a potential mechanism of TBX6-associated CVMs. To further investigate this pathogenetic model, we ascertained and collected 108 Chinese CVM cases and found that 10 (9.3%) of them carried TBX6 null mutations in combination with common hypomorphic variants at the second TBX6 allele. For in vivo functional verification and genetic analysis of TBX6 compound inheritance, we generated both null and hypomorphic mutations in mouse Tbx6 using the CRISPR-Cas9 method. These Tbx6 mutants are not identical to the patient variants at the DNA sequence level, but instead functionally mimic disease-associated TBX6 variants. Intriguingly, as anticipated by the compound inheritance model, a high penetrance of CVM phenotype was only observed in the mice with combined null and hypomorphic alleles of Tbx6. These findings are consistent with our experimental observations in humans and supported the dosage effect of TBX6 in CVM etiology. In conclusion, our findings in the newly collected human CVM subjects and Tbx6 mouse models consistently support the contention that TBX6 compound inheritance causes CVMs, potentially via a gene dosage-dependent mechanism. Furthermore, mouse Tbx6 mutants mimicking human CVM-associated variants will be useful models for further mechanistic investigations of CVM pathogenesis in the cases associated with TBX6.


Assuntos
Anormalidades Congênitas/genética , Escoliose/genética , Coluna Vertebral/anormalidades , Proteínas com Domínio T/genética , Adolescente , Alelos , Animais , Sistemas CRISPR-Cas/genética , Criança , Pré-Escolar , Anormalidades Congênitas/diagnóstico por imagem , Anormalidades Congênitas/fisiopatologia , Modelos Animais de Doenças , Feminino , Haploinsuficiência , Humanos , Lactente , Masculino , Camundongos , Mutação , Fenótipo , Escoliose/diagnóstico por imagem , Escoliose/fisiopatologia , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/fisiopatologia
11.
J Hum Genet ; 63(11): 1119-1128, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30115950

RESUMO

Intracranial vertebral-basilar artery dissection (IVAD) is an arterial disorder leading to life-threatening consequences. Genetic factors are known to be causative to certain syndromic forms of IVAD. However, systematic study of the molecular basis of sporadic and isolated IVAD is lacking. To identify genetic variants contributing to the etiology of IVAD, we enrolled a cohort of 44 unrelated cases with a clinical diagnosis of isolated IVAD and performed whole-exome sequencing (WES) for all the participants; a trio exome sequencing approach was used when samples from both parents were available. Four previously reported disease-causing heterozygous variants (three in COL3A1 and one in FBN1) and seven novel heterozygous variants in IVAD-related genes were identified. In addition, six variants in novel IVAD genes including two de novo heterozygous nonsynonymous variants (each in VPS52 and CDK18), two stop-gain variants (each in MYH9 and LYL1), and two heterozygous biallelic variants in TNXB were considered to be possibly contributing to the phenotype, with unknown significance according to the existing knowledge. A significantly higher mutational rate of IVAD candidate genes was observed in patients versus our in-house controls (P = 0.002) (DISCO study, http://www.discostudy.org/ , n = 2248). Our study provided a mutational landscape for patients with isolated IVAD.


Assuntos
Aneurisma Dissecante/genética , Exoma , Sequenciamento de Nucleotídeos em Larga Escala , Aneurisma Intracraniano/genética , Adulto , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Estudos de Coortes , Colágeno Tipo III/genética , Feminino , Fibrilina-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Motores Moleculares/genética , Cadeias Pesadas de Miosina/genética , Proteínas de Neoplasias/genética
12.
J Med Genet ; 55(10): 675-684, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30120215

RESUMO

BACKGROUND: Brain arteriovenous malformations (BAVM) represent a congenital anomaly of the cerebral vessels with a prevalence of 10-18/100 000. BAVM is the leading aetiology of intracranial haemorrhage in children. Our objective was to identify gene variants potentially contributing to disease and to better define the molecular aetiology underlying non-syndromic sporadic BAVM. METHODS: We performed whole-exome trio sequencing of 100 unrelated families with a clinically uniform BAVM phenotype. Pathogenic variants were then studied in vivo using a transgenic zebrafish model. RESULTS: We identified four pathogenic heterozygous variants in four patients, including one in the established BAVM-related gene, ENG, and three damaging variants in novel candidate genes: PITPNM3, SARS and LEMD3, which we then functionally validated in zebrafish. In addition, eight likely pathogenic heterozygous variants (TIMP3, SCUBE2, MAP4K4, CDH2, IL17RD, PREX2, ZFYVE16 and EGFR) were identified in eight patients, and 16 patients carried one or more variants of uncertain significance. Potential oligogenic inheritance (MAP4K4 with ENG, RASA1 with TIMP3 and SCUBE2 with ENG) was identified in three patients. Regulation of sma- and mad-related proteins (SMADs) (involved in bone morphogenic protein (BMP)/transforming growth factor beta (TGF-ß) signalling) and vascular endothelial growth factor (VEGF)/vascular endotheliual growth factor recepter 2 (VEGFR2) binding and activity (affecting the VEGF signalling pathway) were the most significantly affected biological process involved in the pathogenesis of BAVM. CONCLUSIONS: Our study highlights the specific role of BMP/TGF-ß and VEGF/VEGFR signalling in the aetiology of BAVM and the efficiency of intensive parallel sequencing in the challenging context of genetically heterogeneous paradigm.


Assuntos
Proteínas Morfogenéticas Ósseas/genética , Variação Genética , Malformações Arteriovenosas Intracranianas/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Fator de Crescimento Transformador beta/genética , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Animais Geneticamente Modificados , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , China , Estudos de Coortes , Modelos Animais de Doenças , Família , Feminino , Heterozigoto , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/patologia , Masculino , Transdução de Sinais , Sequenciamento Completo do Exoma , Peixe-Zebra
13.
J Orthop Surg Res ; 13(1): 140, 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29880007

RESUMO

BACKGROUND: Osteoporotic vertebral compression fracture (OVCF) is a common type of fracture, and percutaneous kyphoplasty (PKP) is an eligible solution to it. Previous studies have revealed that both the volume and filling pattern of bone cement correlate with the clinical outcomes after PKP procedure. However, the role of bone cement distribution remains to be illustrated. METHODS: To retrospectively evaluate the relationship between the bone cement distribution and the clinical outcomes of unilateral PKP, we enrolled 73 OVCF patients receiving unilateral PKP treatment. All the intervened vertebrae were classified into three groups based on the bone cement distribution observed on postoperative X-ray films. Preoperative and postoperative radiographic parameters including the vertebral height and kyphotic Cobb angle were recorded, and anterior vertebral height restoration rate (AVHRR) and Cobb angle correction (CR) were then calculated to assess the vertebral height reconstruction. Preoperative and postoperative Oswestry Disability Index (ODI) and visual analogue scale (VAS) were adopted by interviewing patients to assess the mobility improvement and pain relief. Demographic data, body mass index (BMI), lumbar bone mineral density (evaluated by BMD T-score) of each patient, bone cement volume (BV), and bone cement extravasation (BE) were also recorded. Between- and within-group comparisons and multivariable correlation analysis were carried out to analyze the data. RESULTS: VAS and ODI scores were both significantly improved in all of the enrolled cases with no significant differences between groups. Among the three groups, the average age, AVHRR, and BV were significantly different. Occurrence of BE was significantly different between two of the three groups. AVHRR was demonstrated to correlate negatively with preoperative anterior vertebral height ratio and positively with preoperative Cobb angle, CR, diffusion score, and ODI changes. CONCLUSIONS: Bone cement distribution is a potential predictor to the reconstructive effects in unilateral PKP for OVCFs. Bone cement distribution is associated with AVHRR and BV, as well as the risk of BE occurrence. Greater bone cement distribution may indicate better vertebral restoration along with a higher BE risk.


Assuntos
Cimentos para Ossos , Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Idoso , Feminino , Fraturas por Compressão/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral , Resultado do Tratamento
14.
Respir Res ; 19(1): 47, 2018 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-29580282

RESUMO

BACKGROUND: Asthma-chronic obstructive pulmonary disorder (COPD) overlap (ACO) is characterized by the coexistence of features of both asthma and COPD and is associated with rapid progress and a poor prognosis. Thus, the early recognition of ACO is crucial. OBJECTIVES: We sought to explore the plasma levels of biomarkers associated with asthma (periostin, TSLP and YKL-40), COPD (NGAL) and their possible correlation with lung function, the bronchodilator response and radiographic imaging in patients with asthma, COPD and with features of ACO. METHODS: We enrolled 423 subjects from 6 clinical centers. All participants underwent blood collection, lung function measurements, bronchodilator response tests and high-resolution CT. Correlations of the plasma biomarkers with lung function, the bronchodilator response and percentemphysema were calculated by Spearman's rank correlation and multivariate stepwise regressionanalysis. RESULTS: 1) Patients with features of ACO had lower plasma YKL-40 than COPD patients and a moderate elevated plasma level of NGAL compared with asthma patients. 2) Patients with features of ACO had an intermediate degree of airflow obstruction, the bronchodilator response and emphysema between patients with COPD and asthma. 3) Plasma YKL-40 was negatively correlated with lung function and with the bronchodilator response, and plasma NGAL was positively correlated with the extent of emphysema. CONCLUSIONS: Plasma YKL-40 is a promising candidate for distinguishing between patients with features of ACO and COPD patients, while plasma NGAL may be a valuable biomarker for differentiating between patients with features of ACO and asthma patients. CLINICAL TRIAL REGISTRATION: ChiCTR-OOC-16009221.


Assuntos
Asma/sangue , Asma/diagnóstico , Proteína 1 Semelhante à Quitinase-3/sangue , Lipocalina-2/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade
15.
Oncotarget ; 8(43): 74276-74286, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-29088784

RESUMO

MicroRNA-146a-5p (miR-146a) functions as a tumor suppressor or oncogene involved in multiple biological processes. But, the underlying molecular mechanisms by which miR-146a contributes to osteosarcoma (OS) remain unclear. The correlation of miR-146a expression with clinicopathologic characteristics and prognosis of OS patients was analyzed by Kaplan-Meier and Cox regression analysis. Cell growth in vitro and in vivo was assessed by MTT, cell colony formation and animal models. The target of miR-146a was identified by bioinformatics software and gene luciferase reporter. As a result, miR-146a expression was substantially elevated in OS tissues and was positively associated with the tumor size (P=0.001) and recurrence (P=0.027) of OS patients. Moreover, knockdown of miR-146a suppressed cell proliferation and colony formation in vitro and in vivo. In addition, zinc and ring finger 3 (ZNRF3) was identified as a direct target of miR-146a in OS cells, and was negatively correlated with miR-146a expression in OS tissues. Overexpression of ZNRF3 inhibited cell growth and rescued the tumor-promoting role of miR-146a via inhibition of GSK-3ß/ß-catenin signaling pathway. Taken together, miR-146a may function as an oncogene in OS cells by targeting ZNRF3/GSK-3ß/ß-catenin signaling pathway, and represent a promising biomarker for OS patients.

16.
J Cell Biochem ; 118(10): 3061-3071, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28590031

RESUMO

Based on the tremendous progress of the understanding on the CRISPR-Cas systems, the application CRISPR/Cas technology has been extended into increasing scenarios in biological and biomedical investigation. The potency of gene editing has been greatly improved by the rapid development of engineered Cas9 variants and modified CRISPR platforms. As advanced sequencing technology identified vast causative genetic basis for human diseases, CRISPR toolkits are now able to mediate precise genetic disruption or correction in vitro and in vivo. In this review, we have discussed the recent development of the CRISPR/Cas gene-editing technology and the extensive applications of the CRISPR platforms in biological and biomedical investigation, including disease modeling in animal and human cell line, development of gene therapy, as well as high-throughput genetic screening. J. Cell. Biochem. 118: 3061-3071, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Edição de Genes , Terapia Genética/métodos , Animais , Terapia Genética/tendências , Humanos
17.
J Interpers Violence ; 32(8): 1249-1266, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-26025344

RESUMO

The present study examined dispositional hope as a potential mediator of the association between sexual assault and negative affective conditions, namely, depressive and anxious symptoms in a sample of 223 female college students. Results from conducting bootstrapped mediation analyses indicated that hope agency, but not hope pathways, mediated the link between sexual assault victimization and negative affective conditions in females. Importantly, the associations of sexual assault with both depressive and anxious symptoms remained highly significant independent of hope. Some implications of the present findings are discussed.


Assuntos
Vítimas de Crime/psicologia , Esperança , Delitos Sexuais , Estudantes/psicologia , Universidades , Adolescente , Adulto , Depressão/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Autorrelato , Delitos Sexuais/psicologia , Estados Unidos , Adulto Jovem
18.
J Psychol ; 150(3): 333-41, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25970325

RESUMO

This study examined the role of hope in understanding the link between loneliness and negative affective conditions (viz., anxiety and depressive symptoms) in a sample of 318 adults. As expected, loneliness was found to be a significant predictor of both anxiety and depressive symptoms. Noteworthy, hope was found to significantly augment the prediction of depressive symptoms, even after accounting for loneliness. Furthermore, we found evidence for a significant Loneliness × Hope interaction effect in predicting anxiety. A plot of the interaction confirmed that the association between loneliness and anxiety was weaker among high, compared to low, hope adults. Some implications of the present findings are discussed.


Assuntos
Ansiedade/psicologia , Depressão/psicologia , Solidão/psicologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
20.
Soc Work ; 60(3): 211-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26173362

RESUMO

In this study, authors examined basic psychological needs (namely, competence, autonomy, and relatedness) as potential mediators of the association between sexual assault and depressive symptoms in a sample of 342 college students. Results from conducting a multiple mediation test provided support for partial mediation involving the indirect effects of competence and autonomy. In contrast, no support for mediation was found involving relatedness. It is notable that sexual assault remained a significant predictor of depressive symptoms in students. Therefore, findings indicate how sexual assault may both directly and indirectly (through psychological needs) lead to greater depressive symptoms in students. Authors concluded the article with a discussion of the implications of their findings for expanding the study of basic psychological needs in college students and the need for greater efforts to prevent and treat sexual assault on campus.


Assuntos
Depressão/etiologia , Delitos Sexuais/psicologia , Adolescente , Adulto , Depressão/diagnóstico , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sudeste dos Estados Unidos , Universidades , Adulto Jovem
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